A PARP1-ERK2 synergism is required for the induction of LTP

L. Visochek, G. Grigoryan, A. Kalal, H. Milshtein-Parush, N. Gazit, I. Slutsky, A. Yeheskel, A. Shainberg, A. Castiel, R. Seger, M. F. Langelier, F. Dantzer, J. M. Pascal, M. Segal, M. Cohen-Armon

Research output: Contribution to journalArticlepeer-review

Abstract

Unexpectedly, a post-translational modification of DNA-binding proteins, initiating the cell response to single-strand DNA damage, was also required for long-term memory acquisition in a variety of learning paradigms. Our findings disclose a molecular mechanism based on PARP1-Erk synergism, which may underlie this phenomenon. A stimulation induced PARP1 binding to phosphorylated Erk2 in the chromatin of cerebral neurons caused Erk-induced PARP1 activation, rendering transcription factors and promoters of immediate early genes (IEG) accessible to PARP1-bound phosphorylated Erk2. Thus, Erk-induced PARP1 activation mediated IEG expression implicated in long-term memory. PARP1 inhibition, silencing, or genetic deletion abrogated stimulation-induced Erk-recruitment to IEG promoters, gene expression and LTP generation in hippocampal CA3-CA1-connections. Moreover, a predominant binding of PARP1 to single-strand DNA breaks, occluding its Erk binding sites, suppressed IEG expression and prevented the generation of LTP. These findings outline a PARP1-dependent mechanism required for LTP generation, which may be implicated in long-term memory acquisition and in its deterioration in senescence.

Original languageEnglish
Article number24950
JournalScientific Reports
Volume6
DOIs
StatePublished - 28 Apr 2016

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